Repository of Research and Investigative Information

Repository of Research and Investigative Information

Zahedan University of Medical Sciences

S100A8/9 induces cell death via a novel, RAGE-independent pathway that involves selective release of Smac/DIABLO and Omi/HtrA2

(2008) S100A8/9 induces cell death via a novel, RAGE-independent pathway that involves selective release of Smac/DIABLO and Omi/HtrA2. Biochimica Et Biophysica Acta-Molecular Cell Research. pp. 297-311. ISSN 0167-4889

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Official URL: <Go to ISI>://WOS:000253270200014

Abstract

A complex of two S 100 EF-hand calcium-binding proteins S100A8/A9 induces apoptosis in various cells, especially tumor cells. Using several cell lines, we have shown that S100A8/A9-induced cell death is not mediated by the receptor for advanced glycation endproducts (RAGE), a receptor previously demonstrated to engage S 100 proteins. Investigation of cell lines either deficient in, or over-expressing components of the death signaling machinery provided insight into the S100A8/A9-mediated cell death pathway. Treatment of cells with S100A8/A9 caused a rapid decrease in the mitochondrial membrane potential (Delta Psi(m)) and activated Bak, but did not cause release of apoptosis-inducing factor (AIF), endonuclease G (Endo G) or cytochrome c. However, both Smac/DIABLO and Omi/HtrA2 were selectively released into the cytoplasm concomitantly with a decrease in Drp1 expression, which inhibits mitochondrial fission machinery. S100A8/A9 treatment also resulted in decreased expression of the anti-apoptotic proteins Bcl2 and Bc1-X-L, whereas expression of the pro-apoptotic proteins Bax, Bad and BNIP3 was not altered. Over-expression of Bcl2 partially reversed the cytotoxicity of S100A8/A9. Together, these data indicate that S100A8/A9-induced cell death involves Bak, selective release of Smac/DIABLO and Omi/HtrA2 from mitochondria, and modulation of the balance between pro- and antiapoptotic proteins. (C) 2007 Elsevier B.V. All rights reserved.

Item Type: Article
Keywords: Bcl2 protein family S100/calgranulin cancer regression Drp1 receptor for advanced glycated endproducts (RAGE) mitochondrial fission XIAP cytochrome-c release calcium-binding proteins glycation end-products mitochondrial fission arachidonic-acid intermembrane space caspase activation endothelial-cells membrane protein serine-protease Biochemistry & Molecular Biology Cell Biology
Page Range: pp. 297-311
Journal or Publication Title: Biochimica Et Biophysica Acta-Molecular Cell Research
Journal Index: ISI
Volume: 1783
Number: 2
Identification Number: https://doi.org/10.1016/j.bbamcr.2007.10.015
ISSN: 0167-4889
Depositing User: خانم مهدیه رضائی پور
URI: http://eprints.zaums.ac.ir/id/eprint/2865

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